1. Technical Field
This description relates to methods and materials involved in modulating (e.g., increasing or decreasing) Toll-like receptor activity.
2. Background Information
The Toll family of polypeptides is remarkably conserved across the taxonomic kingdoms. This family includes the invertebrate Toll polypeptides, the vertebrate Toll-like receptors, and the plant resistance genes (Hoffmann and Reichhart, (2002) Nat. Immunol., 3:121-126; Akira et al., (2001) Nat. Immunol., 2:675-680; and Hulbert et al., (2001) Annu. Rev. Phytopathol., 39:285-312). Many of these polypeptides have homologous domains and signaling pathways, which are used to trigger inflammatory and immunological responses. However, the function of these proteins extends beyond host defense.
As expressed on leukocytes, endothelial cells, and various parenchymal cells, Toll-like receptor 4 (TLR4) detects the products of microorganisms, such as lipopolysaccharide (LPS), and endogenous substances, such as heparan sulfate and hyaluronic acid. Following detection of these substances, TLR4 transduces signals leading to activation of NFκB, among other signaling pathways (Takeda et al., Annu. Rev. Immunol., 21:335-376 (2003)), that induce the expression of genes that incite inflammation and adaptive immunity. These responses sequester and clear microorganisms and heighten resistance of the host upon re-infection (Akira et al., Nat. Immunol., 2:675-680 (2001) and Krutzik et al., Curr. Opin. Immunol., 13:104-108 (2001)).